Many promising drugs are under investigation for the treatment of neurological disorders (NDs). Once demonstrated to be effective, suitable delivery strategies will be needed to deploy drugs to their targets inside the brain. Drugs targeted to the central nervous system typically have very low success rates in clinical studies due to poor penetration across the blood brain barrier (BBB). The BBB maintains homeostasis in the brain but poses a significant challenge for drug delivery. Current delivery methods are highly invasive and carry significant risk of brain damage. We propose to develop a novel drug delivery system that can facilitate the delivery of therapeutics to the brain. Our strategy is based on using endogenous human transferrin (hTf) as a carrier protein for drug delivery. Human Tf is highly abundant in blood, has a long circulation half-life, and can easily enter the brain via receptor mediated transcytosis. We specifically propose to use Serum Transferrin Attaching Peptides (STrAPs), previously discovered in our group, to non-covalently tag drugs to hTf in systemic circulation. Owing to its high concentration and long plasma half-life, hTf can sustain large drug doses in circulation for extended time periods, and assist in their continuous delivery to the brain. We propose two specific aims to achieve our objective. In specific aim 1, we propose to identify STrAPs from a library of previously discovered sequences that bind to hTf with very high affinity and specificity, and do not compete with the interactions between hTf and its natural receptor hTfR. In specific aim 2, we propose to test STrAPs for their ability to deliver model drugs (dextrans) and a representative drug (nerve growth factor, NGF) across an in vitro model of the human BBB. If successful, the proposed project will have a tremendous impact on the clinical success of central nervous system therapeutics that are under development as well as those that have dropped out from Phase I/II clinical studies due to poor brain bioavailability. Our proposed work will provide the preliminary validation of STrAPs in vitro, and provide the necessary motivation to conduct in vivo studies in animal models of NDs using NGF as an active drug.